DESCRIPTION: (Applicant's Abstract) Cigarette smoking is a prototypic case of drug dependence and a dominant cause of coronary artery disease (CAD). In the past several decades, women's rates of CAD and other smoking-related diseases have increased in proportion to their increased exposure to tobacco smoking. Effective smoking cessation interventions have the enormous potential of reducing smoking prevalence and improving women's health. The proposed studies provide a direct and logical extension of our previous research evaluating smoking cessation and relapse prevention (RP) treatments in health-compromised women. Our ongoing work fails to provide strong evidence of RP's superiority over a comparison treatment, and underscores the need to develop more potent interventions to prevent relapse in this refractory population. We propose to do this by combining RP with a new effective and safe pharmacologic intervention. Two parallel, double-blind, placebo-controlled studies will be conducted, each employing a 2 X 2 factorial design that crosses medication (bupropion 300 mg/d vs. placebo) and therapy (RP vs. Discussion Support). Women who smoke will be randomized into one of the four treatment combinations. The 7-week trial will involve weekly clinic visits at which time participants will receive medication doses and individual therapy. The integrated treatment of RP and bupropion 300 mg/d is expected to increase significantly the probability of abstinence and produce improvements in other relevant domains, including self-efficacy, coping, craving, and depressive symptomatology. Study 1 will enroll 104 women with stable CAD. Study 2 will enroll 104 women with significant CAD risk factors, but without diagnosis. The studies are technically rigorous and scientifically innovative. An analogue role-play test will be used to examine coping skills acquisition as a function of treatment and as a predictor of outcome. To verity treatment fidelity we will use written therapy manuals, trained therapists, and adherence checking systems. Appropriate procedures to safeguard against adverse events will include initial medical evaluation, baseline ECG, daily recording of pill taking and cardiac symptoms using an electronic medication dispensing and diary unit, weekly measurement of vital signs and side effects, and regular contact with the study psychiatrist and cardiologist. The primary dependent measure will be smoking status, validated by saliva cotinine. Assessments at 3-, 6-, 9-, and 12-months following maintenance treatment will be used to evaluate the relative durability of treatment effects. In summary, this research will contribute new theoretical and empirical information concerning the independent and interactive effects of two proven interventions, and shed light on the processes by which these interventions work. We expect that this study will result in the development of an efficacious treatment for smoking in medically at-risk women, and will therefore have major implications for health and health care costs related to drug dependence and medical disorders.